Variations in activation energy and nuclei size during nucleation explain chiral symmetry breaking.

We show that variations in enantiomer nuclei size and activation energy during the nucleation stage of crystallization are responsible for the chiral symmetry breaking resulting in excess of one of the possible enantiomers with respect to the other. By understanding the crystallisation process as a non-equilibrium self-assembly process, we quantify the enantiomeric excess through the probability distribution of the nuclei size and activation energy variations which are obtained from the free energy involved in the nucleation stage of crystallisation. We validate our theory by comparing it to Kondepudi et al. previous experimental work on sodium chlorate crystallisation. The results demonstrate that the self-assembly of enantiomeric crystals provides an explanation for chiral symmetry breaking. These findings could have practical applications for improving the production of enantiopure drugs in the pharmaceutical industry, as well as for enhancing our understanding of the origins of life since enantiomeric amino acids and monosaccharides are the building blocks of life.

Chiral symmetry breaking induced by energy dissipation.

Spontaneous chiral symmetry breaking is observed in a wide variety of systems on very different scales, from the subatomic to the cosmological. Despite its generality and importance for a large number of applications, its origin is still a matter of debate. It has been shown that the existence of a difference between the energies of the intermediate states of optical enantiomers leads to disparate production rates and thus to symmetry breaking. However, it is still unclear why this occurs. We measured for the first time the optical rotation angle of NaClO3 enantiomeric crystals in solution during their formation and found that the amount of energy needed to induce the enantiomeric excess is exactly the same as the energy dissipated per mole of solid salt calculated from the entropy production obtained from the proposed model. The irreversible nature of the process leading to entropy production thus explains the chiral symmetry breaking in the salt crystals studied. The proposed method could be used to explain the formation of self-organised structures generated by self-assembly of enantiomers arising from chiral symmetry breaking, such as those emerging in the production of advanced materials and synthetic biological tissues.

Self-assembling outside equilibrium: emergence of structures mediated by dissipation.

A set of disordered interacting building blocks may form ordered structures by means of a self-assembling process. An external intervention in the system by adding a chemical species or by applying forces leads to different self-assembly scenarios with the appearance of new structures. For instance, the formation of microtubules, gels, virus capsides, cells and living beings among others takes place by self-assembly under nonequilibrium conditions. A general evolution criterion able to account for why nature selects some structures outside equilibrium and not others is lacking. Nevertheless, progress in the understanding of nonequilibrium self-assembly (NESA) mechanisms has been made thanks to the formulation of models that take particular situations into consideration. We review recent efforts devoted to describing self-assembly out of equilibrium and we provide a reference linking several current concepts in order to help in the development of new models and experimental studies. We hope that the knowledge of the intimate mechanisms leading to the formation of structures will make the implementation of re-configurable and bio-inspired materials possible and give a simpler perspective on the understanding of the emergence of life.

Measurement invariance of the driving inattention scale (ARDES) across 7 countries.

The Attention-Related Driving Errors Scale (ARDES) is a self-report measure of individual differences in driving inattention. ARDES was originally developed in Spanish (Argentina), and later adapted to other countries and languages. Evidence supporting the reliability and validity of ARDES scores has been obtained in various different countries. However, no study has been conducted to specifically examine the measurement invariance of ARDES measures across countries, thus limiting their comparability. Can different language versions of ARDES provide comparable measures across countries with different traffic regulations and cultural norms? To what extent might cultural differences prevent researchers from making valid inferences based on ARDES measures? Using Alignment Analysis, the present study assessed the approximate invariance of ARDES measures in seven countries: Argentina (n = 603), Australia (n = 378), Brazil (n = 220), China (n = 308). Spain (n = 310), UK (n = 298), and USA (n = 278). The three-factor structure of ARDES scores (differentiating driving errors occurring at Navigation, Manoeuvring and Control levels) was used as the target theoretical model. A fixed alignment analysis was conducted to examine approximate measurement invariance. 12.3 % of the intercepts and 0.8 % of the item-factor loadings were identified as non-invariant, averaging 8.6 % of non-invariance. Despite substantial differences among the countries, sample recruitment or representativeness, study results support resorting to ARDES measures to make comparisons across the country samples. Thus, the range of cultures, laws and collision risk across these 7 countries provides a demanding assessment for a cultural-free inattention while-driving. The alignment analysis results suggest that ARDES measures reach near equivalence among the countries in the study. We hope this study will serve as a basis for future cross-cultural research on driving inattention using ARDES.

Pigmentary mosaicism as a recurrent clinical manifestation in three new patients with mosaic trisomy 12 diagnosed postnatally: cases report and literature review.

BACKGROUND: To date, only twenty-one cases diagnosed postnatally with mosaic trisomy 12 have been reported. The most frequent phenotypic manifestations are developmental delay, dysmorphic facial features, congenital heart defects, digital alterations, and pigmentary disorders. In the present report, detailed clinical and genetic profiles of three unrelated new patients with mosaic trisomy 12 are described and compared with previously reported cases. CASE PRESENTATION: In the present report, we include the clinical, cytogenetic, and molecular description of three Mexican patients diagnosed postnatally with mosaic trisomy 12. At phenotypic level, the three patients present with developmental delay, dysmorphic facial features, congenital heart defects and skin pigmentary anomalies. Particularly, patient 1 showed unique eye alterations as bilateral distichiasis, triple rows of upper lashes, and digital abnormalities. In patient 2 redundant skin, severe hearing loss, and hypotonia were observed, and patient 3 presented with hypertelorism and telecanthus. Hyperpigmentation with disseminated pigmentary anomalies is a common trait in all of them. The cytogenetic study was carried out under the strict criteria of analysis, screening 50-100 metaphases from three different tissues, showing trisomy 12 mosaicism in at least one of the three different tissues analyzed. With SNParray, the presence of low-level mosaic copy number variants not previously detected by cytogenetics, and uniparental disomy of chromosome 12, was excluded. STR markers allowed to confirm the absence of uniparental disomy as well as to know the parental origin of supernumerary chromosome 12. CONCLUSIONS: The detailed clinical, cytogenetic, and molecular description of these three new patients, contributes with relevant information to delineate more accurately a group of patients that show a heterogeneous phenotype, although sharing the same chromosomal alteration. The possibility of detecting mosaic trisomy 12 is directly associated with the sensitivity of the methodology applied to reveal the low-level chromosomal mosaicism, as well as with the possibility to perform the analysis in a suitable tissue.

Genetic and clinical characterization of 73 Pigmentary Mosaicism patients: revealing the genetic basis of clinical manifestations.

BACKGROUND: Pigmentary mosaicism constitutes a heterogeneous group of skin pigmentation alterations associated with multisystem involvement. The aim of this study was to establish a complete cytogenetic and molecular characterization of PM patients, emphasizing on searching for possible low chromosomal mosaicism and on establishing an accurate genotype-phenotype correlation. RESULTS: A total of 73 patients were included (3 months to 18 years of age), 52% male and 48% female. Observed in 69 (95%) patients, the most frequent pattern of pigmentation was fine and whorled BL, which was associated with disseminated skin extent in 41 (59%) patients. Central nervous system (84%) alterations were the most frequent observed in the group of patients, followed by the musculoskeletal (53%) and ophthalmologic (27%) alterations. Considering the pattern of pigmentation, no significant differences in association with skin extent or extracutaneous manifestations were detected. Following a strict cytogenetic analysis strategy, screening metaphases from three different tissues (peripheral blood, hyperpigmented and hypopigmented skin) we found that 23/73 patients had chromosomal abnormalities classified as follows: 1) Mosaic with 2 or more different cell lines with structural alterations n = 19; 2) Polyploidy (mosaic) n = 1 and 3) Alterations in all cells in three different tissues n = 3. SNP array, array CGH and FISH were useful for the complete characterization of the chromosomal aberrations, for the detection of microdeletions in patients with normal karyotype but with strong clinical suspicious of chromosomal alteration, and for a better establishment of genotype-phenotype correlation. In 2 patients we found genes associated with some of the extracutaneous manifestations (SHH, MNX1, PPP2R2C). CONCLUSIONS: This group of 73 patients finely described is the largest series of patients with pigmentary mosaicism reported worldwide. As we showed in this study, the followed analysis strategy allowed the detection of cytogenetic and molecular abnormalities, and made possible the establishment of genotype-phenotype associations in some patients. An important limitation of our study was the analysis of fibroblasts cultures instead of melanocytes and keratinocytes. In some cases the direct molecular DNA analysis of skin biopsy could be another choice.

Mek1/2 gene dosage determines tissue response to oncogenic Ras signaling in the skin.

Ras genes are commonly mutated in human cancers of the skin and other tissues. Oncogenic Ras signals through multiple effector pathways, including the Erk1/2 mitogen-activated protein kinase (MAPK), phosphatidylinositol-3 kinase (PI3K) and the Ral guanine nucleotide exchange factor (RalGEF) cascades. In epidermis, the activation of oncogenic Ras induces hyperplasia and inhibits differentiation, features characteristic of squamous cell carcinoma. The downstream effector pathways required for oncogenic Ras effects in epidermis, however, are undefined. In this study, we investigated the direct contribution of Mek1 and Mek2 MAPKKs to oncogenic Ras signaling. The response of murine epidermis to conditionally active oncogenic Ras was unimpaired by deletion of either Mek1 or Mek2 MAPKKs individually. In contrast, Ras effects were entirely abolished by combined deletion of all Mek1/2 alleles, whereas epidermis retaining only one allele of either Mek1 or Mek2 showed intermediate responsiveness. Thus, the effects of oncogenic Ras on proliferation and differentiation in skin show a gene dosage-dependent requirement for the Erk1/2 MAPK cascade at the level of Mek1/2 MAPKKs.